RNA-Dependent Protein Kinases

  • Raymond A. Petryshyn
  • Sergie Nekhai
  • Evelio D. Perez-Albuerne
Part of the Endocrine Updates book series (ENDO, volume 16)


RNA molecules conduct various functions in living organisms by interacting with other biological molecules. The recognition of RNA molecules, usually by proteins, is often dependent on the shape into which the RNA folds, rather than on any specific nucleotide sequence (1). This review focuses on double-stranded RNA (dsRNA) dependent protein kinase (PKR), which phosphorylates the a subunit of eukaryotic initiation factor-2 (eIF-2α) (2). PKR contains two amino acid sequence motifs called dsRNA-binding motifs (DRBM that allow binding to dsRNA and subsequently convert the protein from a latent to an active serine/threonine protein kinase (3). PKR is the only known kinase that depends on dsRNA for activation, although two closely related eIF-2a kinases, pancreatic eIF-2α kinase (PEK) (4) and PKR-like endoplasmic reticulum kinase (PERK) (5), have been described. PKR presents a unique paradigm for studying RNA: protein interaction because its activity depends on binding to dsRNA but not DNA, single-stranded RNA, or RIVA:DNA hybrids. Well-known for mediating the antiviral effects of interferons (IFNs), PKR is also implicated in regulating cell differentiation, signal transduction, and in eliciting apoptosis in response to various stress induction agents (3, 6). Although the protein is ubiquitous in cells, PKR activity is suppressed during cell proliferation and in tumor cells, suggesting a role for the kinase in the regulation of cell proliferation. This review summarizes the viral and cellular proteins and dsRNAs that activate and inhibit PKR, and the most recent findings in PKR knockout mice.


Human Immunodeficiency Virus Type Dependent Protein Kinase Homeostatic Regulation Pseudosubstrate Inhibition 
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Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Raymond A. Petryshyn
    • 1
  • Sergie Nekhai
    • 2
  • Evelio D. Perez-Albuerne
    • 3
  1. 1.National Cancer InstituteBethesdaUSA
  2. 2.Howard UniversityUSA
  3. 3.Children’s National Medical CenterUSA

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